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Published on: January 7, 2019
Antisense inhibition of chondrocyte CD44 expression leading to cartilage chondrolysis
G Chow1, J J Nietfeld, C B Knudson
1Rush Medical College, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612, USA.
Objective:
To better define critical functions of the hyaluronan receptor CD44 in cartilage.
Methods:
Articular chondrocytes and cartilage tissue slices were treated with CD44 sequence-specific antisense phosphorothioate oligonucleotides. CD44 expression was probed by immunofluorescence microscopy, enzyme-linked immunosorbent assay, and Western blotting.
Results:
Antisense oligonucleotides demonstrated a dose- and time-dependent inhibition of CD44 protein expression; negative controls showed no effect. Similar to osteoarthritic cartilage, antisense-treated cartilage slices displayed a near-total loss of stainable proteoglycan-rich matrix.
Conclusion:
CD44 expression is needed for maintenance of cartilage homeostasis.
Insights
Hyaluronan receptor CD44 (cluster of differentiation 44) is crucial for maintaining cartilage health. Inhibiting CD44 expression in cartilage leads to significant matrix loss, similar to osteoarthritis.
Area of Science:
- Biochemistry
- Molecular Biology
- Orthopedics
Background:
- Cartilage degradation is a hallmark of osteoarthritis.
- The role of the hyaluronan receptor CD44 (cluster of differentiation 44) in cartilage homeostasis is not fully understood.
Purpose of the Study:
- To elucidate the critical functions of CD44 in articular cartilage.
Main Methods:
- Articular chondrocytes and cartilage tissue slices were treated with CD44-specific antisense oligonucleotides.
- CD44 expression levels were assessed using immunofluorescence microscopy, ELISA, and Western blotting.
Main Results:
- Antisense treatment resulted in dose- and time-dependent inhibition of CD44 protein expression.
- Cartilage slices treated with antisense oligonucleotides showed a substantial loss of proteoglycan-rich matrix, resembling osteoarthritic cartilage.
Conclusions:
- CD44 expression is essential for maintaining cartilage homeostasis.
- Targeting CD44 may offer therapeutic potential for cartilage repair.
